Pyridine-alkynyl Compounds for mGluR5 Antagonism
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Solution Overview
Problem
Current treatments for pain, urinary incontinence, addictive disorders, Parkinson's disease, anxiety, epilepsy, seizures, strokes, pruritic conditions, cognitive disorders, Huntington's chorea, ALS, dementia, retinopathy, muscle spasms, migraines, dyskinesia, and depression are inadequate due to side effects and limited efficacy.
Innovation Solution
Development of Pyridine-alkynyl Compounds that inhibit mGluR1 and mGluR5 receptors, which are administered to treat or prevent these conditions by reducing aberrant somatosensory processing and modulating glutamate activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional analgesics (non-opioid or opioid) are administered to treat pain, then pain relief is achieved, but side effects increase and therapeutic profile deteriorates
Solution Approach 1:
The patent introduces mGluR5 receptor antagonists as intermediary compounds that mediate pain relief through a different mechanism than traditional analgesics. These compounds act as mediators between the nervous system and pain pathways, blocking metabotropic glutamate receptor 5 to achieve analgesia without the harmful side effects of opioids and non-opioid analgesics
Solution Approach 2:
The patent changes the pharmacological parameter from traditional analgesic mechanisms (COX inhibition, opioid receptor activation) to mGluR5 receptor antagonism. This parameter change in the mechanism of action allows for effective pain relief while avoiding the side effect profile associated with conventional analgesics
2Reliability
If anticholinergics are administered to treat urinary incontinence, then bladder-detrusor-muscle overactivity is controlled, but adverse side effects increase and patient compliance decreases
Solution Approach 1:
The patent introduces mGluR5 receptor antagonists as intermediary compounds that mediate bladder control by blocking metabotropic glutamate receptor 5 in the bladder and nervous system. This intermediary mechanism provides bladder-detrusor-muscle control without the anticholinergic side effects that plague traditional treatments
3Reliability
If existing treatments for neurological and psychiatric conditions are administered, then some therapeutic effect is achieved, but side effects limit efficacy and quality of life
Solution Approach 1:
The patent introduces mGluR5 receptor antagonists as versatile intermediary compounds that can mediate therapeutic effects across multiple neurological and psychiatric conditions including anxiety, depression, epilepsy, and cognitive disorders. The single mechanism of mGluR5 blockade serves as a unified intermediary approach to treat diverse conditions with improved side effect profiles
Solution Approach 2:
The patent demonstrates the universal applicability of mGluR5 receptor antagonists across multiple therapeutic areas. A single class of compounds targeting mGluR5 provides multi-functional benefits for treating pain, urinary incontinence, anxiety, depression, epilepsy, and cognitive disorders, replacing the need for condition-specific medications with problematic side effects
Data Source
AI summary
The invention provides a compound of formula (I):(where R1, Q, A and R2 are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Pyridine-alkynyl Compound”); pharmaceutical compositions comprising an effective amount of a Pyridine-alkynyl Compound; and methods for treating or preventing a condition such as pain, urinary incontinence, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, a seizure, stroke, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Pyridine-alkynyl Compound.